Non-Blood Contacting Mechanical Device That Improves Heart Function After Injury

ABSTRACT

A method and device are provided for non-blood contact mechanically assisting an injured (e.g., infarcted) ventricle by coupling an inflatable bladder or other volume adjustable device to the injured ventricle and selectively inflating the bladder or increasing the size of the volume in systole to apply force against the injured ventricle and deflating the bladder or reducing the size of the volume in diastole to remove force against the injured ventricle. When no mechanical assistance is being provided to the injured ventricle, the inflatable bladder or volume adjustable device is preferably maintained at a predetermined pressure so as to selectively stiffen the injured tissue and alter ventricular geometry a desired amount. The method is implemented by a mechanical assist device including the volume adjustable device, a coupling means that couples the volume adjustable device to the injured ventricle, a pulsatile device that selectively increases and decreases the volume of the volume adjustable device, and a controller responsive to the pace of the heart and adapted to selectively change the size of the volume adjusting device in different modes of operation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 16/299,679, filedMar. 12, 2019, which is a continuation of U.S. Ser. No. 14/361,502,filed May 29, 2014 (now abandoned), which is the National Stage ofInternational Application No. PCT/US2012/067410, filed Nov. 30, 2012,which claims the benefit of U.S. Provisional Application No. 61/565,780,filed Dec. 1, 2011, the entire contents of each of which areincorporated herein by reference for any and all purposes.

TECHNICAL FIELD

The invention relates to a mechanical device that is affixed to aportion of the ventricular epicardial surface to improve the function ofthe heart after it has experienced an injury such as a myocardialinfarction.

BACKGROUND

Myocardial infarction as well as other injuries and diseases lead tostructural changes in the heart that result in the alteration of infarct(injured tissue) material properties and ventricular geometry. Followingthe injury, necrotic myocardium and the normal extracellular matrix arereplaced by a disarranged collagen network, which ultimately leads toscar formation. These histologic and cellular changes that occurdirectly alter the mechanical stiffness of the injured myocardial tissueand surrounding non-injured myocardium (border zone). Theoretical leftventricular (LV) modeling and experimental data from animal experimentshave demonstrated that material properties of the injured area and itsgeometry have a profound effect on global and regional ventricularfunction that occur immediately after the injury and progress inseverity over time.

Progressive impairment in cardiac function after injury is due not onlyto a loss of contracting myocardium but also to the short-term andlong-term mechanical and biologic effects of the injury on the normallyperfused myocardium. While injured tissue material properties(elastance) have been theoretically predicted to have significanteffects on cardiac performance, surprisingly little is known about thechanges in material properties that occur as the injury heals. It hasbeen hypothesized that increased material elastance (reduction instiffness), which has been demonstrated to occur during injury healingand maturation, contributes to the progressive loss of global cardiacfunction experienced by many patients after myocardial infarction (MI).

Ischemic cardiomyopathy is associated with a multitude of chronicchanges to the geometry, function, and biomechanics of the failingventricle. Infarct expansion results in progressively enlarging adynamicor hypokinetic myocardium which can significantly alter the fluiddynamics within the ventricle. Early studies utilizing conductancecatheter-based LV pressure-volume loops have shown that infarctionraises the “zero-pressure volume” within the ventricle (i.e.,V₀)—increasing the amount of functional dead space. This dead spacepermits an increasing portion of the blood in the LV to reside in anarea that has impaired contractile function while better functioningportions of the heart remain relatively unloaded. Newer evidence fromvelocity-encoded 3D MRI also supports the formation of abnormal flowpatterns within the left ventricle as the heart remodels-resulting in anincreasing amount of retained blood within the ventricle (i.e., residualvolume). These abnormal flow patterns can reduce the hearts contractileefficiency, impair mitral valve function and increase the risk of bloodclot formation in the heart. The inventors have hypothesized thatrestoring or normalizing physiologic flow patterns may improve leftventricular mechanics and efficiency, improve mitral valve function, andreduce the risk of blood clot embolization. While many invasivetherapies have been described for the treatment of ischemic heartfailure (see, e.g., George et al., Prog. Cardiovasc. Disease (2011),Vol. 54, pp. 115-131), few have been designed to alter left ventricularresidual volume (or V₀) or LV blood flow patterns by directly changingthe mechanics and geometry of the pathologic myocardium.

The increased elastance (reduced stiffness) in the injured area of theheart results in increased mechanical stress in the injured region. Thisincrease in stress alters how the injured area heals. The type andamount of collagen that is produced during injury healing is negativelyinfluenced by elevated mechanical stress in the injured area. Theinventors have demonstrated that limiting mechanical stress in theinjured area improves healing and increases stiffness in the injuredarea.

Currently, the inventors are aware of no methods to variably adjustregional infarct elastance, LV geometry, or to perform regionalassistance to the infarcted (injured) region of the heart. Injectablematerials and cell therapies have been directed at this clinical problembut cannot be easily optimized in a patient specific manner or provideactive assistance in addition to infarct stiffening. These techniquesalso cannot influence material properties and ventricular geometry tothe extent that the proposed invention would be capable ofaccomplishing.

It is thus desired to stiffen the injured tissue (infarct) in-vivo toimprove function and mitigate remodeling and to develop an in-vivomethod of altering injured tissue (infarct) elastance and geometry andto provide assistance in synchrony with remote myocardial contraction.The present invention addresses these needs in the art.

SUMMARY

The invention addresses the above-mentioned needs in the art byproviding an epicardial assist device that can actively assist injuredmyocardium in synchrony with remote myocardial contraction and improveinjured tissue (infarct) elastance and ventricular residual volume andgeometry in response to remote myocardial contraction. The injuredtissue (infarct) is stiffened in-vivo by coupling the injured (infarct)region to an elastic fluid fill chamber, such as an inflatable bladder,and then varying the volume in the fluid fill chamber to alter theinjured tissue material properties. The device so configured has beenshown to provide diminished ventricular remodeling and improved LVfunction as evidenced by the improvement in end-systolic volume andejection fraction.

In an exemplary embodiment, the invention provides a mechanical devicethat is affixed to a portion of the ventricular epicardial surface toimprove the function of the heart after it has experienced an injurysuch as a myocardial infarction. The device can be operated in activemode, passive mode or both simultaneously. In passive mode, the devicecan variably stiffen the injured tissue (infarct) to variably alter theventricular geometry and eliminate the volume of blood contained by thedyskinetic injured region in both diastole and systole. In diastole, thepassive device acts to shift the blood volume to the more normallyfunctioning contractile regions of the ventricle that are remote fromthe injury. This improves contractility in these remote regions based onStarlings Law of the Heart. In systole, the passive device prevents thedyskinetic region from acting as a capacitor (energy sink) that absorbscontractile energy that would otherwise go into driving blood out theaortic valve during the injection phase of the cardiac cycle. On theother hand, the active mode produces two effects in systole: 1) directassistance to the injured tissue (infarct) region augmenting systolicejection (the device imparts energy directly to the circulation) and 2)further reduction of the capacitor (energy sink) effect that is producedby the dyskinetic injured region. During diastole in active mode, thedevice promotes ventricular filling by a suction effect. This increasedventricular performance is again based on Starlings Law of the Heart.

Methods of mechanically assisting an injured heart ventricle inaccordance with exemplary embodiments of the invention include the stepsof coupling an elastic fluid fill chamber, such as an inflatablebladder, to the injured ventricle and selectively adjusting the chambervolume by, for example, inflating the bladder in systole to apply forceagainst the injured ventricle and by, for example, deflating the bladderin diastole to remove force against the injured ventricle. In a staticmode of operation, the pressure of the fluid fill chamber is maintainedat a predetermined pressure so as to selectively stiffen the injuredventricle a desired amount. In static mode operation, the fluid fillchamber variably alters a geometry of the injured ventricle to apre-injury shape by eliminating a cavity volume of the ventricle boundedby the injured ventricle tissue. The inflatable fill volume alsoredirects blood volume from a non-contractile injured region of theventricle to a contractile remote region of the ventricle.

The mechanical assist device for providing active assistance to aninjured ventricle in accordance with the inventive method includes in anexemplary embodiment an elastic fill chamber such as an inflatablebladder, means for coupling the fill chamber to the injured ventricle,means for adjusting the volume in the fill chamber, such as a pneumaticunit that selectively inflates and deflates a bladder, and a controlunit responsive to the pace of the heart and adapted to selectivelyincrease the volume of the fill chamber (e.g., inflate the bladder) insystole to apply force against the injured ventricle and to decrease thevolume of the fill chamber (e.g., deflate the bladder) in diastole toremove force against the injured ventricle. In an exemplary embodiment,the means for selectively adjusting the volume of the fill chamberincludes a controller responsive to the pace of the heart and adapted toselectively expand the volume of the fill chamber in systole to applyforce against the injured ventricle and to selectively reduce the volumeof the fill chamber in diastole to remove force against the injuredventricle. In an embodiment in which the fill chamber is a bladder, afluid fill port selectively fills the bladder with fluid under controlof a pulsatile device responsive to the controller. In a static mode,the fill chamber is maintained at a predetermined volume to selectivelystiffen the injured ventricle and/or to alter the ventricle geometry adesired amount.

In exemplary embodiments, the fill chamber is adapted to be implanted ina patient on epicardial tissue so as not to contact blood being pumpedby the patient's heart. The fill chamber also may have an inelasticouter shell to direct force from the fill chamber towards the ventricle.The fill chamber is coupled to the epicardial tissue using any of anumber of suitable means such as sutures.

The fill chamber may include a single bladder, a bladder having a firstportion for accepting a first fluid and a second portion for accepting asecond fluid provided by first and second fill ports, or a plurality ofbladders adapted to accept fluid from a plurality of fluid fill ports.The fluid may be a gas or a liquid.

In exemplary embodiments, the mechanical assist device operates in aplurality of operational modes. For example, the means for selectivelyadjusting the volume of the fill chamber is adapted to operate in astatic mode where the fill chamber is affixed over the injured ventricleand filled with fluid to a predetermined volume, a synchronous dynamicmode that times expansion and reduction of the fill volume with thecardiac cycle, and/or an asynchronous dynamic mode in which anamplitude, frequency, and/or duration of the adjustment of the volume ofthe fill chamber is adjusted independent of the cardiac cycle.

In alternative embodiments, the fill chamber may be replaced by a solidmaterial configured to change size of the ventricle when affixed to theinjured tissue so as not to contact blood being pumped by the patient'sheart. This material is coupled to the heart adjacent the injured tissueand functions to selectively stiffen the injured tissue and/or to alterventricle geometry a desired amount over time. The solid material may beindividualized for a patient by appropriate selection of the position,size, and volume of the solid material.

BRIEF DESCRIPTION OF THE DRAWINGS

The various novel aspects of the invention will be apparent from thefollowing detailed description of the invention taken in conjunctionwith the accompanying drawings, of which:

FIGS. 1A-1C illustrate an epicardial surface showing an infarct area, asingle bladder design for a fluid fill chamber, and an outer shell thatmay be a polypropylene mesh or an inelastic outer shell that restrainsthe bladder against the infarct region in accordance with the invention.FIG. 1A is a perspective view, FIG. 1B is a side view, and FIG. 1C is arear view.

FIGS. 2A-2C illustrate an epicardial surface showing an infarct area, adual bladder design for a fluid fill chamber, and an outer shell thatmay be a polypropylene mesh or an inelastic outer shell that restrainsthe bladders against the infarct region in accordance with theinvention. FIG. 2A is a perspective view, FIG. 2B is a side view, andFIG. 2C is a rear view.

FIGS. 3A-3C illustrate a multi-bladder design for a fluid fill chamberand an outer shell that may be a polypropylene mesh or an inelasticouter shell that restrains the bladders against the infarct region inaccordance with the invention. FIG. 3A is a rear view, FIG. 3B is a sideview, and FIG. 3C is a rear view.

FIG. 4A illustrates an MRI image of the heart in device static modewhere the device is affixed over the infarct region and filled withfluid.

FIG. 4B is a graph showing that infarct strain significantly decreasesin device static mode indicating that the device has stiffened theregion, resulting in less stretch and dyskinetic motion.

FIG. 5 illustrates ultrasound images of the heart in device static modefollowing an infarct at end-diastole and end-systole to illustrate thatthe geometry of the left ventricle becomes abnormal (0 ml) due toaltered regional material properties and contractility and that fillingthe device restores the left ventricular geometry to a more normal shapeand dimensions (8 ml).

FIG. 6A illustrates maximal principal strain and LV deformation in aninfarcted animal at bladder volumes of 0 mL and 8 mL for a sliceadjacent to the infarct and an apical slice remote from the infarct.

FIG. 6B is a graph showing that in device static mode filling the deviceshifts the volume from the dead space to the remote myocardium,increasing loading and strain production.

FIG. 7A illustrates an embodiment for implementing a synchronous dynamicmode using a pulsatile device responsive to a programmed controller. Thepulsation of the device is timed to the measured cardiac cycle using acardiac gating signal as illustrated in FIG. 7B.

FIGS. 8A-8E illustrate the effect of synchronized dynamic mode onregional flow when an assist device is placed at the arrow positionwhereby diastolic flow velocity increases with device activation at FIG.8A compared to non-assist at FIG. 8B. Flow in systole is also increasedwith activation at FIG. 8C compared to unassisted at FIG. 8D. Theactivation of the assist device produces positive flow in systolepropelling blood out of the heart while rapid deflation of the deviceduring diastolic filling (FIG. 8A and FIG. 8B) creates diastole negativeflow (suction effect on nearby blood) which augments filling as shown atFIG. 8E, resulting in flow velocities over 150 cm/s towards theventricular wall, while rapid inflation of the device during earlysystole (FIG. 8C and FIG. 8D) forces volume away from the infarct atapproximately 100 cm/s, and, in doing so, eliminates intraventricularvolume surrounded by adynamic myocardium.

FIGS. 9A and 9B illustrate an embodiment for implementing anasynchronous dynamic mode using a pulsatile device responsive to aprogrammed controller. The amplitude, frequency, and duration of thepulsation of the device can be adjusted as desired and is notsynchronized to the cardiac cycle as illustrated in FIG. 9B.

FIG. 10 illustrates a model used to optimize the static and dynamicdevice for specific patient application. The device is modeled usingfinite element analysis and is coupled to the heart finite element model(FEM) and lumped parameter model of the cardiovascular system.

FIG. 11 illustrates placement of the assist device on an infarct of theheart using minimally invasive surgical techniques.

FIG. 12 illustrates placement of the assist device on an infarct of theheart using transcutaneous techniques.

FIG. 13 illustrates placement of the assist device on the infarct viatranscutaneous techniques where the assist device is in the form of awire mesh that is collapsed for insertion into a delivery sheath and isplaced via a subxiphoid approach.

FIGS. 14A and 14B illustrate the influence of the assist device on MRand LV vortex formation without assist at FIG. 14A and with assist atFIG. 14B.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The invention will be described in detail below with reference to FIGS.1-14. Those skilled in the art will appreciate that the descriptiongiven herein with respect to those figures is for exemplary purposesonly and is not intended in any way to limit the scope of the invention.All questions regarding the scope of the invention may be resolved byreferring to the appended claims.

In order to variably adjust the injured tissue (infarct) elastance andLV geometry in-vivo, the device 10 of FIGS. 1A-1C has been developedthat couples the injured tissue (e.g. infarct) to a coupling means 12such as an external mesh forming a composite material or an inelasticouter shell made of, for example, ePTFE or Dacron. The device 10 ofFIGS. 1A-1C couples the injured tissue to the external mesh or inelasticouter shell 12 using a fluid fill chamber (e.g., bladder) 14 made of,for example, silicone, PET, urethane, or nylon, and placed between theinjured tissue area and the external polypropylene mesh or inelasticouter shell 12. The external mesh or inelastic outer shell 12 is heldagainst the injured tissue (infarct) region by suturing the externalmesh or inelastic outer shell 12 to the epicardial surface of the heartusing, for example, sutures 16 and cell adhesion promoters 18. Inaddition, an implantable (subcutaneous) fill port may be exteriorizedthat allows the fluid fill chamber 14 to be connected to an externalpneumatic or other volume adjustment device for adjustment of the volumeof the fluid fill chamber and thus injured tissue stiffness. Of course,mesh or an inelastic outer shell 12 is not necessary. Any coupling meansthat may couple, attach, or fix the fluid fill volume to a specifiedepicardial region is all that is needed. The coupling means may beinelastic, partially elastic, or directionally elastic in order tocustomize the treatment. Also, the device does not necessarily need toinclude a fluid filled bladder. A solid (e.g., egg-shaped) materialconfigured to change LV size when affixed to the heart in the area ofinjury could achieve the intended result. Preoperative stress modelingbased on MRI, echocardiography and/or other imaging tests could be usedto design the solid object based on an individual patient's heart shape.A self-expanding wire mesh device constructed of stainless steel ornitinol could also be designed to achieve a similar result. FIG. 13illustrates an assist device is in the form of a wire mesh.

In exemplary embodiments, the fluid fill chamber 14 includes one or moreinflatable bladders 14. The inflatable bladder 14 can consist of asingle bladder 14 with one filling chamber as shown in FIGS. 1A-1C. Asingle fill port 20 is connected to the bladder 14 to adjust its size byadding or removing of fluid or gas. The mesh or inelastic outer shell 12is attached to the bladder 14 and is used for attachment and as abuttress to direct the force inward towards the epicardium.

Alternatively, the fluid fill chamber 14 may include a dual bladderconfiguration including a bladder with a partition creating twoindependent sections 14′ and 14″ as shown in FIG. 2. One section 14′ isfilled with fluid and is used in the static mode to stiffen the heartand to adjust geometry. An independent fill port 20′ is attached to thestatic bladder section 14′ to adjust volume. The other section 14″ isfilled with a gas and is used in the dynamic mode to assist the heart.It has an independent fill port 20″ to provide cyclic volume changes.Attached to the outer surface of the dual bladder is a mesh or aninelastic shell 12 to direct force inward.

To allow for in situ adjustment, a multiple bladder device system hasbeen developed. It consists of multiple small and large bladders 14′″arranged in the same plane (FIGS. 3A and 3B). Each bladder 14′″ has itsown fill port 20 that is connected to a manifold 22. Removing bladders14′″ and sealing the port 20 to that specific bladder 14′″ only canadjust the size of the device 10. Bladders 14′″ of various sizes,shapes, and number can be used in the device 10 of FIGS. 3A and 3B.

The device 10 can function in at least three different modes: static,synchronous dynamic, and asynchronous dynamic. It can operate in asingle mode or any combination of the three simultaneously orconsecutively depending on need.

Static mode includes the device volume remaining constant at apredetermined value and only being altered when required to adjusteffect on cardiac function. This mode is used to stiffen the regionunder the device decreasing regional strain (FIG. 4). FIG. 4Aillustrates an image of the heart in device static mode where the deviceis affixed over the infarct region and filled with fluid. FIG. 4B is agraph showing that infarct strain significantly decreases in devicestatic mode indicating that the device has stiffened the region,resulting in less stretch and dyskinetic motion. Regional and globalgeometry is altered from an abnormal shape to a more normal shape usingthis mode (FIG. 5). FIG. 5 illustrates images of the heart in devicestatic mode following an infarct at end-diastole and end-systole toillustrate that the geometry of the left ventricle becomes abnormal (0ml) due to altered regional material properties and contractility andthat filling the device restores the left ventricular geometry to a morenormal shape and dimensions (8 ml) (see description of FIG. 6 below).Also, volume is shifted from dead space bounded by the abnormal geometryto the remote regions increasing loading and strain. The static modealso effects wound healing by decreasing static and cyclic strain. Largecyclic or static strain has been shown to decrease fibroblaststimulation to produce collagen resulting in a more compliant infarct.

Synchronous dynamic mode, on the other hand, includes filling the device10 in a manner that is cyclically synchronized to the native heartcontraction (see description of FIG. 7 below). This mode providespartial assist without blood contact moving the blood out of thedevice-applied region during systole and augmenting filling duringdiastole (see description of FIG. 8 below). This mode adds energy to thesystem and decreases the workload of the heart.

Asynchronous dynamic mode provides non-heart synchronized volumepulsations at various amplitudes, frequencies, and durations (FIG. 9).FIG. 9A illustrates an embodiment for implementing an asynchronousdynamic mode using a pulsatile device responsive to a programmedcontroller. The amplitude, frequency, and duration of the pulsation ofthe device can be adjusted as desired and is not synchronized to thecardiac cycle as illustrated in FIG. 9B. This mode cyclically altersstrain in both the device-applied region and the remote non-devicecontact regions. Strain amplitude, frequency, and duration alter woundhealing and material properties changing the regional stiffness of theheart. For example, high frequency, low amplitude adjustments that arenot synchronized with the heart beat may affect the healing process byslightly moving the heart tissue and potentially improving tissuecharacteristics through slight movement of the otherwise restrainedinfarcted tissue. Fibroblasts have been shown to respond to cyclic lowamplitude strain by increasing collagen production and tissue tensilestrength.

The device of FIG. 1 was assessed using a swine infarct model. A 20%posterolateral infarct was created and the device was placed over theinfarct region. Five days post infarction the animal was imaged using a3T MRI scanner (Siemens TIM Trio). Left ventricular volume and strainwere measured at baseline and at a bladder volume of 8 ml using a 3DSPAMM tagged pulse sequence. Image analysis was performed using anoptical flow method (OFM). Langranian strain results were determinedfrom which the 3D principal strains where calculated. Left ventricularvolumes were measured from long-axis 3D TrueFISP images.

FIG. 6A illustrates maximal principal strain and LV deformation in aninfarcted animal at bladder volumes of 0 mL and 8 mL for a sliceadjacent to the infarct and an apical slice remote from the infarct. Inthe figure, adjacent remote refers to the non-infarcted region in thesame short access slice, while apical remote refers to a region at theapex of the heart that is furthest from the infarct. FIG. 6B is a graphshowing that in device static mode filling the device shifts the volumefrom the dead space to the remote myocardium, increasing loading andstrain production. It will be appreciated by those skilled in the artthat FIG. 6A illustrates short axis slices demonstrating maximumprincipal stain vector magnitude. Maximum principal strain in the remoteregion adjacent to the infarct improved (0.08 (0 ml) versus 0.095 (8ml)) when the bladder 14 was inflated from 0 ml to 8 ml. Infarctprincipal strain decreased with bladder inflation (0.04 (0 ml) versus0.02 (8 ml)) indicating infarct stiffening. Remote apical strain alsoimproved with inflation (0.07 (0 ml) versus 0.085 (8 ml)). The change instrain and the observed alteration of the LV geometry with bladderinflation is confirmation of the shift volume from the akinetic infarctregion to the contractile remote region. Left ventricular volumes at 0ml were 91.6 mL (EDV—end diastolic volume) and 59.7 mL (ESV—end systolicvolume), 31.9 mL (SV—stroke volume) and 34.8% (EF—ejection fraction). At8 mL, left ventricular volumes were as follows: 87.7 mL (EDV), 46.7 mL(ESV), 41.0 mL (SV) and 46.7% (EF). The device 10 was shown to acutelyincrease infarct stiffness in a graded fashion and to reduce infarctdyskinetic movement. An improved contractile function and less LVremodeling out to 4 weeks after infarction was observed.

When the device 10 was deflated in these experiments 4 weeks afterinfarction it was found that the infarct remained stiff, there was nobulging of the infarct as was seen in the untreated controls. Thisfinding demonstrated that the infarct had healed differently as a resultof the 4 weeks of restraint. This is analogous to a bone healing whileit is rendered immobile by a cast or splint. Reduction in injury stressimproved healing and caused the infarct to be permanently stiffened bythe temporary restraint.

In this large animal model, total elastance of the infarct area wasaltered by coupling the infarct to an external mesh 12 via an inflatablebladder 14. The induced increased elastance was transmitted over theinfarct and border zone region resulting in altered maximal principalstrain magnitude and direction. Altering strain direction in the borderzone from stretch to thickening combine with the decreased infarctstretch was found to have a positive effect on attenuating myocardialremodeling and infarct expansion.

To determine the effect of the device 10 of FIG. 1 with cyclicstiffening on LV function, a group of animals received a posterolateralinfarct with the device 10 placed at the time of infarct creation. Anexteriorized port 20 connected the bladder 14 to a pneumatic pulsatiledevice 30 controlled by a controller 32 during data and image collectionas shown in FIG. 7, where FIG. 7A illustrates an embodiment forimplementing a synchronous dynamic mode using a pulsatile deviceresponsive to a programmed controller. As shown, the pneumatic pulsatiledevice 30 is responsive an ECG input that provides a cardiac gatedsignal (FIG. 7B) indicative of the atrial pace of the heart and that isported to the pneumatic pulsatile device 30 by controller 32 as a gatingtrigger for bladder inflation and deflation during the heart cycle.

In a passive (static) mode, the bladder is inflated by a pneumatic driveunit to an optimal level for the individual patient and varied over timein accordance with the desired stiffness of the infarct region. However,in accordance with an exemplary embodiment, the device may beselectively inflated/deflated by the pneumatic drive device in responseto outputs from controller 32 at the respective portions of the cardiaccycle (FIG. 7B) so as to provide active assistance during systole anddiastole by producing local deformation of the infarct region via apneumatic pump of the pulsatile device 30 synchronized to the cardiaccycle. The controller 32 and pneumatic drive unit of the pulsatiledevice 30 are powered by a suitable power supply (not shown). Thus, thedevice of FIG. 7 can be used to both passively stiffen the infarct andto produce active assistance.

The device 10 of FIG. 7 has passive and dynamic assist modes. In thepassive mode (i.e., when no inflating/deflating of the bladder 14 inresponse to the atrial pace is conducted), the bladder 14 is filled toan optimal level as determined by ejection fraction and stroke volume.The bladder 14 is continually adjusted to maintain optimal performanceby adding or removing volume as needed. The dynamic mode, on the otherhand, provides direct assistance to the left ventricle. The assistanceis directed to the dyskinetic infarct region, which amplifies the effectof the assist by moving blood out of the dyskinetic region duringsystole and allowing filling during diastole. This aspect not onlyprovides assistance but also decreases left ventricular stress andworkload. The synchronous dynamic mode is synchronized to the cardiaccycle and timing and can be adjusted to optimize left ventricularfunction. The fill pattern can also be modified to alter the rate andduration of inflation and deflation. The device 10 can also function indual passive and dynamic assist mode. This mode varies the passive anddynamic components of the assist to optimally improve left ventricularfunction.

The device of FIG. 7 was tested on five Yorkshire swine that underwentdirect ligation of the circumflex artery via thoracotomy to create aposterolateral myocardial infarction (MI). Twelve weeks post-infarct, acustom-made inflatable neoprene bladder was placed on the transmurallyinfarcted epicardial surface. LV pressures were continuously recordedusing a Millar pressure transducer catheter (Millar Instruments,Houston, Tex.). A pressure-gated, synchronous pulsation device 10 wasconnected to the epicardial bladder and positioned outside the magneticfield. The bladder 14 was then inflated during systole and deflatedduring diastole via rapidly exchanged helium gas. Using a 3.0 T SiemensMAGNETOM Trio A Tim, the animals then underwent cardiac and respiratorygated cardiac MRI. LV volumes with the device 10 off (deflated) andduring active assistance were obtained using a 2D SPGR sequence with thefollowing parameters: TR/TE/FA=24.2 ms/2.4 ms/150, BW=400, FOV=300mm×243 mm, Matrix=192×156, slice thickness=4 mm, Ave.=2, cardiacphases=16-20 depending on heart rate. LV volumes and ejection fraction(EF) were then calculated using ImageJ image analysis software. LVfunction was compared using a paired t-test. 4D phase contrast MRI alsowas safely performed during active mechanical assistance and with noassistance. 4D phase contrast pulse sequence parameters used for thisacquisition were as follows: Venc=75 cm/s, Spatial Resolution=2×2×2 mm,Temporal Resolution=20.8 ms.

When compared with the unassisted state, flow patterns near the assistdevice 10 were found to be significantly altered in both systole anddiastole. During early diastolic filling, rapid deflation of the devicecreated a suction effect on nearby blood-resulting in flow velocitiesover 150 cm/s towards the ventricular wall. FIG. 8 illustrates theeffect of synchronized dynamic mode on regional flow when an assistdevice 10 is placed at the arrow position whereby diastolic flowvelocity increases with device activation at (A) compared to non-assistat (B). Flow in systole is also increased with activation at (C)compared to unassisted at (D). The activation of the assist device 10produces positive flow in systole propelling blood out of the heartwhile rapid deflation of the device 10 during diastolic filling (A andB) creates diastole negative flow (suction effect on nearby blood) whichaugments filling as shown at (E),—resulting in flow velocities over 150cm/s towards the ventricular wall, while rapid inflation of the device10 during early systole (C and D) forces volume away from the infarct atapproximately 100 cm/s, and, in doing so, eliminates intraventricularvolume surrounded by adynamic myocardium.

These findings are in stark comparison to the unassisted ventricle—whereminimal flow is identified in this region throughout the cardiac cycleas shown in the flow profiles of FIG. 8E. As the normal heart fills indiastole, vortices are formed behind the anterior and posterior mitralvalve leaflets that help the valve to close. FIG. 14 illustrates theinfluence of the assist device on MR and LV vortex formation withoutassist at (A) and with assist at (B). The formation of these vortices isdisturbed in the heart after infarction. Application of the restraintdevice 10 normalizes LV vortex formation and improves mitral valveclosure especially in patients with mitral regurgitation that resultsfrom LV remodeling (known as functional mitral regurgitation).

While being assisted, the subject's MRI showed a clear concave deformityover the infarct area during systole, while diastolic geometry waslargely preserved. When compared with non-assist, synchronizedepicardial assistance on the infarct area improved EF dramatically(34.1±7.8% vs. 22.8±9.2%, p=0.02). Similarly, end systolic volume wassignificantly decreased in the assisted group (75.7±25.7 ml vs. 90.3ml±28.8, p=0.01). Stroke volume also increased in the assisted group andshowed a trend towards significance (37.4±4.4 ml vs. 25.0±6.7 ml,p=0.08). End diastolic volume did not change between treatments(113±24.8 ml vs. 115.4±22.1 ml, p=0.5).

The device of FIG. 7 in operation has thus shown that chronic adverseventricular remodeling as a result of myocardial infarction decreasesthe functional (ejected) volume within the ventricle while increasingthe residual volume and V₀. The mechanical assist device 10 of theinvention has been used to dramatically increase ventricular flow nearthe infarcted myocardium during both systole and diastole. By rapidlyinflating the device in systole, the ventricular geometry not onlychanges, but blood volume with a predisposition to stagnation isforcibly moved from the adynamic endocardial surface to the contractileremote regions. During diastole, rapid deflation results in negativepressure being applied to the epicardial surface-which in turn augmentslocal diastolic filling and flow via a suction effect. The mechanicalassist device 10 of the invention thus enables one to change andquantify the flow profile of the failing ventricle which may in turnprovide improved efficiency and function as well as improved mitralvalve function and a reduction in the risk of thromboembolism (thrombusformation occurs in areas of stagnant blood flow).

The assist device 10 of the invention increases efficiency of theinjured heart in both active and passive modes. A positive effect forthe heart is produced that requires little energy consumption by thedevice 10. Increased efficiency is not dependent on energy transfer fromthe device 10 to the heart and circulation which is how conventionalventricular assist devices work. Moreover, by shifting blood in diastoleto the uninjured (or less injured) areas, the contractile reserve ofthese areas may be “recruited” based on Starlings Law of the Heart.Also, the capacitor (energy sink) contribution of the infarct duringsystole may be eliminated. The passive mode can do that and it ispotentiated in the active mode. Moreover, the active mode adds energydirectly to the circulation by forcing blood through the aortic valveduring systole and augments filling of the heart during diastole.

Patient Specific Application

The device sizing, mode, function, and position may be determinedspecifically for each individual patient. FIG. 10 illustrates a modelused to optimize the static device for specific patient application. Thedevice is modeled using finite element analysis and is coupled to theheart FEM and lumped parameter model of the cardiovascular system. Thoseskilled in the art will appreciate that modeling the device 10 combinedwith a coupled lumped parameter model of the cardiovascular system andfinite element model (FEM) of the heart will determine optimal deviceparameters. In the static device mode, the optimal position, size andvolume is determined from the model based on input data from MRI andultrasound. The model optimizes the static mode using the followingparameters: end-diastolic volume, end-systolic volume, stroke volume,ejection fraction, stroke work, O₂ consumption, aortic flow, aorticpressure, mitral valve regurgitation, regional strain, and regionalstress. The parameter model may also be used to identify strain patternsthat are unique to the patient and then simulating those patterns forapplication to the patient in ways that could, for example, improve thepositioning and control of a mitral valve prosthetic device so as toreduce leaflet chordae tension.

The dynamic mode optimization includes contraction timing, amplitude,and waveform. Optimization is performed using a model of the dynamicdevice coupled to the cardiovascular model described above with respectto FIG. 10. The model will optimize dynamic function using theparameters presented above.

Wound Healing

The assist device 10 also can promote wound healing by altering strainand stress on the heart, by redistributing blood to improve efficiency,and preventing pooled blood. Mechanically stiffening the infarct usingthe static device over time decreases stress and strain promoting woundhealing and permanent alteration of the infarct material properties.Cyclic strain in the device asynchronous mode also can promote woundhealing. Mechanical cyclic strain stimulates the wound healing processresulting altered material properties.

Dynamic Contraction Methods

Though the embodiments above primarily discuss use of an inflatablebladder as the elastic fluid fill chamber 14, other types of devices maybe used. For example, dynamic contraction of the device 10 can beperformed by mechanical, chemical, and cellular methods. Mechanicalmethods include pneumatic, electromagnetic, and shape memory alloys.Chemical methods include, for example, carbon nanotubes. Cellularmethods include the use of in vivo native muscle to power the device 10and ex vivo implanted muscle.

Device Implantation

Those skilled in the art will also appreciate that the successfulapplication of the assist device to the heart requires 5 distinct steps:

1. Access (Surgical, Minimal Invasive Surgery (MIS), Percutaneous)

2. Heart Stabilization

3. Device Delivery

4. Device Fixation

5. Device Optimization

Each of these steps will be described in turn.

1. Access

A standard full sternotomy or thoracotomy could be used. This would bemost likely in patients who are having concomitant valve or coronaryartery surgery. On the other hand, a subxiphoid approach using a smallupper abdominal incision made to expose and open the pericardium may beused as illustrated in FIG. 11. Also, a mini-thoracotomy may be used toexpose and enter the pericardium. Either of these latter methods may beperformed with the aid of thoracoscopic surgical technology or roboticsurgical technology. As shown in FIG. 12, a purely percutaneous,transvenous approach could be used to place a restraining device in theright ventricle to stabilize a damaged intraventricular septum. On theother hand, FIG. 13 illustrates placement of an assist device on theinfarct via transcutaneous techniques where the assist device is in theform of a wire mesh that is collapsed for insertion into a deliverysheath and is placed via a subxiphoid approach.

2. Heart Stabilization

Minimally invasive surgical approaches that utilize subxiphoid ormini-thoracotomy approaches could be facilitated by using heart holdingor stabilizing devices that are now currently used for off-pump surgicalcoronary revascularization procedures. Those skilled in the art willappreciate that the assist device of the invention may be applied to theheart in an off-pump beating heart procedure or an on-pump still heartprocedure.

3. Device Delivery

The uninflated or unexpanded device (bladder, balloon or nitinol meshstructure) could be placed in a thin catheter and passed through a smallincision in the chest and pericardium and placed against the desiredportion of the injured heart. This placement could be guided byintraoperative imaging such as fluoroscopy, echocardiography or MRI.Robotic and/or thoracoscopic techniques could be used to aid inminimally invasive delivery.

4. Device Fixation

Sutures may be used to fix the assist device 10 to the heart usingstandard surgical tools as well as sutures placed with thoracoscopic orrobotic surgical tools. Other fixation devices include staples,bioglues, prothrombotic agents, materials that cause inflammation,combination of an intact pericardium and a long tether that is securedin the wound, and the device 10 could be incorporated into any number ofsurgical meshes to facilitate suturing and to encourage attachment tothe myocardium.

5. Optimization

Echocardiography, MRI and or fluoroscopy may be used to optimize degreeand timing of device inflation. The positioning of the device 10 andsize of the device 10 could be optimized based on these imagingtechniques. Also, diagnostic catheter technology (Swan-Ganz catheter)could be used to optimize the device for maximal ejection fraction,stroke volume, cardiac output, reduction in LV size at end systole,reduction in LV wall stress, reduction in regional dyskinetic LV wallmotion, reduction in infarct bulging, and/or improvement in LV vortexshape and distribution.

Applications for Use of Assist Device

As will be apparent from the above description, the assist device of theinvention may be used for numerous therapeutic applications. Forexample, the assist device has potential benefits for patients withchronic impaired LV function (with or without regional wall motionabnormalities) as well as for patients who have suffered an acutemyocardial infarction (heart attack). The assist device also may limitmitral regurgitation in patients with reduced LV function and mitralregurgitation. The device also may normalize blood flow through the LV.

1. Chronic LV Impairment

The device can improve cardiac efficiency by eliminating a cavity volumeof the ventricle bounded by the injured heart tissue thereby redirectingblood volume from a non-contractile injured region of the ventricle to acontractile remote region of the ventricle. This is a staticmodification in the heart's diastolic function to affect an improvementin systolic performance. The device also can provide active mechanicalassistance to the impaired heart by coupling device inflation with thecardiac cycle. This is a dynamic modification in the heart's systolicfunction. These approaches also may be combined.

2. Mitral Regurgitation that Results from LV Remodeling

The device in either active or dynamic state of function can be placedon the surface of the heart to reposition the papillary muscle relativeto the mitral valve annulus thereby relieving mitral valve leaflettethering and reducing valve regurgitation. The device also can alterblood flow within the LV to improve mitral valve closure. Externalrestraint from the device can act to normalize LV vortex formation whichhas been shown to affect mitral valve closure.

3. Acute Myocardial Infarction

The device can be permanently placed over the area of an acutemyocardial infarction early after the MI to reduce mechanical stress inthe infarct and surrounding uninfarcted regions of the heart. Thereduced stress will limit LV dilatation and slow or inhibit the onset ofheart failure. The device also can be placed temporarily to improveinfarct healing so the infarct becomes stiffer. This is analogous tosplinting a bone fracture. Also, by reducing the mechanical stress inthe infarct, even temporarily, improve infarct healing can be improvedand result in a stiffer infarct long-term. The mechanical means ofrestraint can then be removed. The stiffer infarct will prevent orreduce LV dilation and slow or eliminate the progression to heartfailure.

4. Combined Uses

For all the above uses just described, the device could bean adjustableballoon or bladder that could be filled with a fluid to optimize thestatic and/or dynamic benefit of the device for an individual patient.The optimal degree of inflation and timing of inflation for each patientcould be determined by echocardiography or MRI. Also, the balloon orbladder may be constructed to have regional variation in stiffness so asto cause the balloon or bladder to preferentially expand in thepreferred direction (i.e. towards the heart) and not a non-preferreddirection.

5. Static Uses

For the static (passive) uses indicated above, the device could be (inaddition to adjustable balloon or bladder) a fixed solid object whoseshape is customized to the patient and designed to improve cardiacefficiency by eliminating a cavity volume of the ventricle bounded bythe injured heart tissue thereby redirecting blood volume from anon-contractile injured region of the ventricle to a contractile remoteregion of the ventricle. The shape of this device could be optimized forindividual patients based on pre-operative echocardiography and MRI.Computational stress modeling of the heart could also be used to designthe device's shape for individual patients. Stress modeling could bebased on MRI or echocardiographic imaging. A self-expanding nitinol meshdevice would be one way to do this. A solid device may also be used thatis absorbable or that could be removed so as to provide infarctrestraint and promote infarct healing and stiffening. It would beabsorbed after stiffening was complete.

6. Optimization of LV Blood (Vortex Formation)

The assist device of the invention may also be used to improvecontractile efficiency, to improve mitral valve function, and to reducepotential for thrombus formation.

Those skilled in the art will also appreciate that the invention may beapplied to other applications and may be modified without departing fromthe scope of the invention. For example, those skilled in the art willappreciate that the device of FIG. 7 can be used in patients who suffermyocardial infarction to stiffen the infarct region in an adjustablefashion so that the infarct stiffness can be varied to optimize theresults in each patient. The device may be implanted in patients withoutcontacting the patient's blood with non-endotheilized surfaces (i.e.,artificial surfaces), thereby reducing a primary cause of morbidity anddeath as a result of implantation of conventional devices. Those skilledin the art will further appreciate that the assist device of theinvention may be used to treat either ventricle and is not limited touse in the specific applications described herein. Accordingly, thescope of the invention is not intended to be limited to the exemplaryembodiments described above, but only by the appended claims.

What is claimed:
 1. A method for using a mechanical static assist device to provide patient specific optimal adjustment of ventricular geometry of a subject's heart, wherein the mechanical static assist device includes a fluid fill chamber configured to statically stiffen injured ventricular tissue and for being selectively placed over the injured tissue, and a fluid reservoir that is in fluid communication with the fluid fill chamber via a feed line for variably adjusting the volume of the fluid fill chamber at least by supplying a fluid to the fluid fill chamber, the method comprising: obtaining data concerning the subject's heart using magnetic resonance imaging (MRI), ultrasound imaging, or both; and, using the obtained data to set the volume of the fluid fill chamber in order to optimize one or more parameters of ventricular function.
 2. The method according to claim 1, wherein the parameters of ventricular function include ejection fraction, stroke volume, end diastolic volume, end systolic volume, degree or amount of mitral regurgitation, wall strain, wall stress, or any combination thereof.
 3. A method for optimizing the use of a mechanical assist device for providing static assistance to injured tissue of a ventricle of a subject's heart, wherein the mechanical assist device includes a fluid fill chamber configured to statically stiffen the tissue and for being selectively placed over the injured tissue, and a fluid reservoir that is in fluid communication with the fluid fill chamber via a feed line for adjusting the volume of the fluid fill chamber at least by supplying a fluid to the fluid fill chamber, the method comprising: obtaining data concerning the subject's heart using magnetic resonance imaging (MRI) and ultrasound imaging; inputting the obtained data into a subject-specific model that includes a coupled lumped parameter model of the subject's cardiovascular system, a finite element model of the subject's heart to predict optimal device volume, or both; and, using the subject-specific model to optimize the fluid fill chamber of the mechanical assist device.
 4. The method according to claim 3, wherein the subject specific model is used to optimize the position, size, or volume of the fluid fill chamber.
 5. The method according to claim 4, wherein each of the position, size, and volume of the fluid fill chamber is optimized.
 6. The method according to claim 3, wherein the data concerning the subject's heart that is obtained using MRI and ultrasound imaging includes end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, stroke work, O₂ consumption, aortic flow, aortic pressure, mitral valve regurgitation, regional strain, regional stress, or any combination thereof.
 7. The method according to claim 3, wherein the subject specific model is further used to identify and simulate strain patterns in the subject's heart in order to optimize positioning and control of the fluid fill chamber, thereby reducing leaflet chordae tension. 